Tiopronin protects against the nephrotoxicity of cisplatin in the rat

1999 ◽  
Vol 18 (12) ◽  
pp. 713-717 ◽  
Author(s):  
J-G Zhang ◽  
M Viale ◽  
M Esposito ◽  
W E Lindup

1 Tiopronim (N-(2-mercaptopropionyl)-glycine) is a drug with a free thiol (sulphydryl) group that is used clinically. We have reported previously that tiopronin protects rat kidney slices in vitro from the nephrotoxic effects of cisplatin and does not reduce the antitumour activity of cisplatin. Tiopronin has been investigated therefore for its protective effects in rats in vivo. 2 The extent of kidney damage was studied 5 days after the administration of cisplatin. A single injection (i.p.) of cisplatin (6 mg/kg; 20,umollkg) to female Wistar albino rats caused a sustained decrease in body weight and, after 5 days, plasma urea, creatinine and kidney weight were increased. Tiopronin (2.5 mmol/kg, p.o.) ameliorated cisplatin nephrotoxicity when given 1 h before cisplatin. Tiopronin provided marked protection against cisplatin-induced increases in urea (from 237+19 mg to 48+23 mg/100 ml; control: 17+1) and creatinine (from 6.5+0.5 to 1.7+0.5 mg/100 ml control: 1.0 + 0.1). Tiopronin did not, prevent the body weight loss caused by cisplatin. In addition, an intraperitoneal dose (1 mmol/lkg) oftiopronin afforded similar protection to that of an oral dose. Rats that received an i.p. mixture of cisplatin (6 mg/kg) and tiopronin (65 mg/kg) displayed generally less toxicity, as indicated by a small fall in body weight and smaller increases in urea and creatinine and kidney weight. 3 The results show that tiopronin protects against cisplatin-induced nephrotoxicity. Oral administration of tiopronin may be a clinically useful way to prevent cisplatin nephrotoxicity.

2019 ◽  
Vol 10 (3) ◽  
pp. 1720-1729
Author(s):  
Noorul Alam ◽  
Gopal V ◽  
Vasanthi C ◽  
Prabal Kumar Manna

Nerunjil kudineer/Neermulli Kudinner is an official Siddha polyherbal formulation used for the various ailments related to the kidney. Cisplatin is an alkylating agent used in chemotherapy for the treatment of various cancers. Its use is limited due to their nephrotoxicity. In this study nephroprotective effect of Nerunjil kudineer (NK) on cisplatin-induced nephrotoxicity in Wistar albino Rats was studied. Male Wistar albino rats were used for this study. Animals were divided into 5 groups (n=6) as control, Cisplatin control (Single dose 7 mg/Kg i.p on the 7th day), Cisplatin with Cystone (p.o), NK200 and NK400 mg/Kg (p.o) for 10 days. At the end of the study, animals were weighed and sacrificed to estimate the relative kidney weight, serum creatinine and Urea. Kidney tissue was estimated for oxidant-antioxidant parameters (MDA, GSH & SOD) and histology study was carried out. Cisplatin reduced body weight and increased kidney weight significantly (P<0.0001). It deprived the renal function by elevating serum creatinine & urea, MDA and reduction in endogenous antioxidants GSH and SOD significantly (P<0.0001). Cisplatin group exhibited focal tubular necrosis and congested blood vessels in histology study. The standard drug Cystone and NK400 significantly increased the body weight, reduced the kidney weight, normalized the kidney function parameters (Serum Cr and Urea), bolstered antioxidant status and showed a trend towards the recovery of histological alterations. NK showed a dose-dependent activity and higher dose, NK400mg /Kg possessed strong nephroprotective activity, which may be due to the efficient antioxidant potential, which reduces lipid peroxidation and oxidative stress induced by cisplatin. The results strongly suggest that Nerunjil kudineer is an effective nephroprotective drug against Cisplatin induced nephrotoxicity.


1939 ◽  
Vol 69 (3) ◽  
pp. 467-483 ◽  
Author(s):  
Florence Walter ◽  
T. Addis

1. The ratios between the rates of growth of the body and of the heart, kidneys, and liver are approximately uniform between 40 gm. body weight and the body weight at maturity in the albino rat. The male and female hearts grow at 0.75 times the rate of growth of the body, the male kidneys at 0.717 times, the female kidneys at 0.648 times, and the liver at 0.838 times the rate of growth of the body as a whole. 2. Formulas for the prediction of organ weight from body weight were derived from the data on 1591 albino rats kept under constant conditions. 3. A series of experiments in which dietetic and metabolic variables were introduced into otherwise constant conditions showed that the heart weight was not affected by diet, and that both kidney weight and weight of liver protein (used as a measure of effective liver size) varied in the direction of change in the protein content of the diet. Decrease in rate of metabolism induced by thyroidectomy and increase in metabolism following the administration of thyroxin led to a corresponding fall and rise of heart, kidney, and liver protein weight. These results were confirmed in experiments on fasted rats with the exception that under these conditions thyroidectomy did not appreciably decrease liver protein weight relatively to fasted controls. Increase in organ metabolism due to dinitrophenol had no effect on organ weight. 4. When experimental changes alter the composition of the body with respect to fat or water, the comparison of experimental and control organ weights in terms of any one function of body weight is fallacious. 5. Conditions that change kidney weight usually change liver protein weight in the same direction and roughly to the same degree. The possible meaning of two exceptions to this rule is discussed. 6. The observations made are regarded as supporting the hypothesis that, after weaning, change in the weight of the heart, kidney, and liver protein is determined mainly by change in the amount of work done by these organs.


2009 ◽  
Vol 79 (1) ◽  
pp. 48-56 ◽  
Author(s):  
Chaturvedi

In the present study, protective effects of bitter melon (Momordica charantia) extract on lipid peroxidation induced by immobilization stress in rats have been assessed. Graded doses of extract (50, 100, and 150 mg/kg body weight) were administered orally to rats subjected to immobilization stress for two hours for seven consecutive days. Stress was applied by keeping the rats in a cage where no movement was possible. After seven days, rats were killed by decapitation after ether anesthesia. Blood and liver were collected to measure thiobarbituric acid reactive substances, reduced glutathione, and catalase. In vitro effects of M. charantia extract on lipid peroxidation in liver homogenate of normal, control, and rats pretreated with extract were carried out against cumene hydroperoxide-induced lipid peroxidation. Results reveal that in vivo M. charantia inhibited stress-induced lipid peroxidation by increasing the levels of reduced glutathione and activities of catalase. These results were further supported by in vitro results. In vitro inhibition of lipid peroxidation was indicated by low levels of thiobarbituric acid in the liver homogenate from pretreated rats and normal rats when incubated with both cumene hydroperoxide and extract. Inhibition was also noted in the homogenate where the rats were pretreated but the mixture contained no extract. Thus this plant provides protection by strengthening the antioxidants like reduced glutathione and catalase. Inclusion of this plant in the daily diet would be beneficial.


1964 ◽  
Vol 6 (2) ◽  
pp. 169-178 ◽  
Author(s):  
R. V. Large

1. Thirty Suffolk × Half bred lambs were slaughtered at the following ages: two twin lambs at birth and two singles and two twins at 1, 2, 3, 4, 6, 8 and 16 weeks of age.2. The following weights were recorded: live-weight immediately before slaughter; and carcass, head, skin, feet, alimentary tract, heart, liver, kidneys, lungs and trachea, and blood immediately afterwards.3. The alimentary tract was emptied and weighed in four separate parts; reticulo-rumen, omasum-abomasum, small intestine, large intestine.4. The volumes of the reticulo-rumen and the omasum-abomasum were measured by immersing in water and filling the organs with water to 2 cm. pressure.5. The in vitro digestive efficiency of rumen liquor from lambs of 1, 2, 3 and 4 weeks of age was assessed.6. Empty body weight was considered to be valuable in comparing animals of different ages or from different feeding regimes or at different times of the year because variations in gut ‘fill’ were eliminated.7. There were no differences between singles and twins in the relationship of the fresh weights of the parts of the body to empty body weight, except that development of the liver and the blood was rather slower for singles.8. Little evidence was found of a difference in rate of development of the alimentary tract between singles an d twins, although the log an d square root transformation suggested a possible difference in reticulo-rumen size in favour of twins, significant at the 5% level.


1969 ◽  
Vol 11 (3) ◽  
pp. 162-168
Author(s):  
Yasmeen Mahar ◽  
Alisha Qamar ◽  
lnayatullah ◽  
Sarwath Fatimee ◽  
Mohammad Fawad Saeeduddin ◽  
...  

Background:Use of dietary supplements to treat illnesses has increasedtremendously in recentyears.Adrenal gland is one ofthemost commonly damaged endocrine gland in the body, not only by chemical or radiation injuries, but also as a result of differenttypes of stress.Search is underway for use ofnatural foods for protection of adrenal gland from different types ofinsults.Objective: To determine the protective effects of L-arginine on streptozotocin (STZ)-induced adrenal gland injury in albino rats,andto compare its efficacy to insulin.Material and Methods: This prospective experimental study was done at BMSI, JPMC, Karachi. Forty male, healthy albino rats,90-120 days old were segregated into 4 groups. Group A was marked as control, group B was administered STZ, group C and Dwere treated with STZ along with insulin and L-arginine respectively. At the end of study period, i.e., 6 weeks, animals weresacrificed under ether anaesthesia. Tissue from the left adrenal gland was processed for frozen sectioning to observe fat content ofthe adrenal cortex by applying OilRed O stain.Results: Oil Red-0 stained frozen sections revealed closely aggregated fat globules in adrenal cortex of STZ treated group B ascompared to control. Moderate betterment was seen in group C and in group D Oil Red O stained frozen sections as compared toSTZ treated group B.Conclusion: The results ofthe study demonstrated adrenal cortex injury by STZ which ameliorated with concomitant use of insulinandL-arginine. The protection was more pronounced with L-arginine as comparedto insulin.Keywords:STZ, adrenal gland,insulin,L-arginine


2021 ◽  
Vol 15 (11) ◽  
pp. 2938-2941
Author(s):  
Fauzia Qureshi ◽  
Syeda Rizwana Jafri ◽  
Hafiza Sadia Ahmad ◽  
Uzma Waseem ◽  
Ursula Akif ◽  
...  

Background: Ovulation induction with clomiphene citrate in women with infertility has been practiced more than 40% years but in infertile patients this treatment plan proved to be ineffective with multiple complication. Body weight plays an important role modulating reproductive development and functioning. Aim: To observe the effects on body weight of female albino rat after use of clomiphene citrate and letrozole for consecutive 1-4 estrous cycles Method: Eighty four adult female Albino rats were equally divided into three groups for this research. Body weight of each rat was measured before and after the experiment. Vaginal smear cytology of each rat was performed to study different phases of estrous cycle. Control group A was given normal saline orally , In Experimental group B rats were given letrozole (Femara) at dose 5mg/kg orally and in Experimental group C rats were given clomiphene citrate at dose 100ug/kg orally. Results: Significant weight gain is observed in rats taking clomiphene citrate as compared to letrozole Conclusion : Comiphene citrate directly affects the body weight which indirectly reduces the ovulation induction and pregnancy rate. Letrozole is good alternate for ovulation induction and for CC resistant patients. Keywords: Estrous cycle, body weight, citrate and letrozole


1959 ◽  
Vol 197 (5) ◽  
pp. 1128-1130 ◽  
Author(s):  
John F. Thomson ◽  
Florence J. Klipfel

Kidney slices from rats in which one-third of the body water was replaced by D2O showed no impairment of the capacity to accumulate PAH, despite the moribund condition of the animals. In vitro, 100% D2O inhibited PAH uptake by 65%, oxygen consumption by only 15%, during a 1-hour incubation of kidney slices; very little PAH was taken up after the first 30 minutes.


2009 ◽  
Vol 55 (3) ◽  
pp. 219-226 ◽  
Author(s):  
Nahla S. El-Shenawy ◽  
Rasha A. Al-Eisa ◽  
Fawzia El-Salmy ◽  
Omema Salah

Abstract Considering that the involvement of reactive oxygen species (ROS) has been implicated in the toxicity of various pesticides, this study was designed to study the ameliorative effect of Vitamin E (100 mg/kg body weight) on mice (25 - 30 mg) treated with diazinon (32.5 or 16.25 mg/kg body weight) organophosphate insecticide for 14 days. Subchronic DZN exposure and the protective effects of vitamins E (vitE) were evaluated for their effects on haematological indices, the enzymes concerning liver damage [plasma alanine aminotransferase (ALT), aspartate aminotaransferase (AST), alkaline phosphatise (AIP), and some parameters of kidney function (urea and creatinine) in mice. Additionally, the histopathological changes in liver and kidney tissue were examined. The high dose of diazinon (DZNH) decreased the body weight significantly at the end of experiment. Additionally, the liver and kidney were examines for histopathological changes. The high dose of diazinon decreased body weight significantly. Moreover, there was a statistically significant decrease in haemoglobin (Hb), red blood cell (RBC) and hematocrit (Hct) in diazinon-treated mice compared to controls. This decrease was partially remedied in the diazinon-treated group that also received vitE. Damage in the liver and kidney tissues was also evident as elevated plasma ALT, AST, ALP, urea and creatinine. VitE partially counteracts the toxic effect of DZN and repairs tissue damage in the liver and kidney, especially when supplemented to 1/4 LD50 intoxicated animals. Histopathological changes in liver and kidney were observed only in 32.5 mg/kg DZN given group. These results suggest that the effects of DZN are dose dependent. No pathological findings were observed in vitE + DZN treated groups. According to the present study, we conclude that vitE can reduce the detrimental impacts of diazinon on haematological indicies, as well as liver and kidney function.


2012 ◽  
Vol 5 (1) ◽  
pp. 29-37 ◽  
Author(s):  
MA Hossain ◽  
M Mostofa ◽  
D Debnath ◽  
AKMR Alam ◽  
Z Yasmin ◽  
...  

To investigate the antihyperglycemic and antihyperlipidemic effect of Momordica charantia (Karala), the aqueous extract of the Karala fruit was tested on streptozotocin (STZ)-induced diabetic rats. Thirty six albino rats were used in the experiment, 30 diabetic and the remaining six as negative control (T1). Diabetes was induced by administering (injecting) STZ at dose of 55mg/kg body weight. Thirty diabetic animals were randomly divided into five groups such as diabetic control group (T2) without any application of treatment, and groups T3,T4,T5 and T6 were treated with aqueous extract of Karala fruits daily at the doses of 250,    500 and 750mg/kg and glibenclamide (at a dose of 5mg/kg body weight) respectively. The body weight was taken and blood samples were collected from individual animal to determine glucose levels at 15 day interval up to 90 days. In addition, Asparate  Transaminenase(AST), Alanine Transaminenase(ALT), Alkaline Phosphatase(ALP), Total cholesterol (TCh) and Triglyceride (TGA) were determined at day 15 and at the end of the experiment. All three doses of Karala extracts reduced diabetic induced blood sugar and the reduction is comparable with standard glibenclamide (GLM) dose particularly with higher doses Karala extracts (500 and 750mg). Karala also prevented body weight loss due to induced diabetes as did by GLM treatment.. The treatment also resulted in a significant reduction of Asparate Transaminenase(AST), Alanine Transaminenase(ALT), Alkaline Phosphatase(ALP), Total cholesterol (TCh) and Triglyceride (TGA) activities of treated rats when compared to the STZ induced  diabetic rats. Higher doses of Karala (500 and 750mg/kg) are as effective as standard GLM dose on measured variables. This study demonstrated that Karala has hyperglycemia and antihyperlipidemic effect against STZ induced diabetic rats. These findings open the possibility of using Karala extract to treat diabetic animal and human patients although further research is warranted. DOI: http://dx.doi.org/10.3329/jesnr.v5i1.11550 J. Environ. Sci. & Natural Resources, 5(1): 29 - 37, 2012  


2016 ◽  
Vol 94 (3) ◽  
pp. 265-271 ◽  
Author(s):  
Saeed Mehrzadi ◽  
Seyed Kamran Kamrava ◽  
Banafshe Dormanesh ◽  
Manijeh Motevalian ◽  
Azam Hosseinzadeh ◽  
...  

The risk of serious side-effects such as nephrotoxicity is the principal limitation of gentamicin (GEN) therapeutic efficacy. Oxidative stress is considered to be an important mediator of GEN-induced nephrotoxicity. The present study was designed to evaluate the efficacy of the combination of melatonin (MT) plus atorvastatin (ATO) against GEN-induced nephrotoxicity in rats. We utilized 30 male Wistar albino rats allocated in 5 groups, each containing 6 rats: control, GEN (100 mg/kg/day), ATO (10 mg/kg/day) + GEN, MT (20 mg/kg/day) + GEN, and ATO (10 mg/kg/day) plus MT (20 mg/kg/day) + GEN. Kidney weight, serum creatinine and urea concentration, renal ROS, MDA, GSH levels, SOD, and CAT activity were determined. GEN-induced nephrotoxicity was evidenced by marked elevations in serum urea and creatinine, kidney weight, renal ROS, and MDA levels and reduction in renal GSH level, SOD and CAT activity. MT pretreatment significantly lowered the elevated serum creatinine concentration, kidney weight, renal ROS and MDA levels. However ATO could not reduce these parameters, but similarly to MT, it was able to enhance the renal GSH level, CAT and SOD activity. In addition, a combination therapy of MT plus ATO enhanced the beneficial effects of ATO, while not changing the effects of MT effects or even improving them. The present study indicates that a combination therapy of MT plus ATO can attenuate renal injury in rats treated with GEN, possibly by reducing oxidative stress, and it seems that MT can enhance the beneficial effects of ATO.


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